The present invention relates to a nanosecond time-gate spectroscopic diagnosis apparatus.
Conventionally, in relation to the above-described field, the following literature have been known.
(1) Medical Equipment Encyclopedia Edition Committee, ed., xe2x80x9c1987-88 Medical Equipment Encyclopedia,xe2x80x9d pp. 426-436, Sangyo Chosakai
(2) xe2x80x9cEncyclopedia of Medical Sciences,xe2x80x9d pp. 46-50, Kodansha
(3) Takuzo Sato, xe2x80x9cFrom Laser CD Player to X-ray Laser,xe2x80x9d pp. 146-170, Denki Shoin (1987)
(4) Harufumi Kato, Hideki Yamamoto, and Toshimitsu Hiyoshi, xe2x80x9cTherapeutic Effect on Cancer by Photosensitive Substances,xe2x80x9d O plus E, No. 160, pp. 83-88 (1993)
(5) Yusaku Shimaoka, Masato Ohmi, and Masamitsu Haruna, xe2x80x9cNanosecond Stroboscopic Microscope for Laser Ablation of Biological Tissue,xe2x80x9d The Institute of Electronics, Information and Communication Engineers, ME and Bio Cybernetics Study Group, Technical Report of IEICE MBE96-93 (1996)
(6) Yusaku Shimaoka, Mitsuo Nakamura, Masato Ohmi, and Masamitsu Haruna, xe2x80x9cNanosecond Stroboscopic Microscope for Laser Ablation of Biological Tissue,xe2x80x9d Conference on Laser and Electro Optics/Pacific Rim (CLEO/PR""97), Paper FF3, Technical Digest pp. 261-262, Makuhari, Chiba, 1997
Conventionally, in actual medical treatment facilities, infrared CO2 lasers and Nd:YAG lasers, serving as laser scalpels, have been used for incision and coagulation in surgical operations (see literature (1) and (2)).
Laser-induced fluorescence analysis (see the above-describe literature (3) and (4)) has been continually studied as an effective diagnosis method. Henceforth, improvement and utilization of a laser-induced biological reaction as a leading medical technique require collection and accumulation of detailed experimental data, including variations with time of a reaction state in the vicinity of the surface of biological tissue caused by irradiation with a laser pulse, and compositions of substances scattering from the surface, as obtained from analysis.
Physical phenomena such as laser ablation of biological tissue and fluorescence generation therefrom occur within a period on the order of nanosecond or less, as is the case of physical phenomena in inorganic substances (see the above-describe literature (3) and (4)). Therefore, spectroscopic analysis of these phenomena requires an optical measurement techniques with a time resolution on the order of nanosecond. Laser ablation of biological tissue refers to a phenomenon by which biological tissue decomposes thermally or photochemically by irradiation with a laser pulse and evaporates instantly.
The present inventors have already developed a nanosecond stroboscopic microscopy system and have performed dynamic analysis of laser ablation of biological tissue (see the above-described literature (5) and (6)). In the system, through spectral analysis of a light emitting plume, the composition of a biological tissue sample can be elucidated, enabling discrimination between normal and lesioned portions of the tissue. Therefore, plume spectral analysis, along with the fluorometric analysis technique, is expected to become a key technology for optical biopsy.
In stroboscopic analysis using a monochromator (see the above-described literature (6)), which is one of several emission spectral analysis techniques, measurement at one particular wavelength can be performed through irradiation with a single laser pulse. Therefore, stroboscopic analysis requires a long time for measurement of plume emission spectra, resulting in damage to the sample being analyzed, and application of such an analysis to a clinical setting is considered to be problematic.
In view of the foregoing, the object of the present invention is to provide a nanosecond time-gate spectroscopic diagnosis apparatus which performs instant spectroscopic analysis of a light emitting plume through irradiation of a biological tissue sample with a single laser pulse, by use of a photo multi-channel analyzer comprising a high-speed gate image intensifier having a gate width on the order of nanosecond.
To achieve the above object, the present invention provides the following:
(1) A nanosecond time-gate spectroscopic diagnosis apparatus wherein a laser pulse from a light source is radiated onto biological tissue in a focused manner, a light emitting plume (a spindle-shaped light emitting substance) generated from the surface of the tissue due to laser ablation is spectroscopically measured at a time gate on the order of nanosecond, and the composition of the tissue is analyzed on the basis of the plume spectra, to thereby diagnose lesion or anomaly of the tissue, the apparatus comprising: a shutter disposed between the light source and a lens opposed to biological tissue; a multi-channel spectrometer (polychromator) for detecting the light emitting plume; a photodetector for detecting a portion of the laser pulse from the light source; an oscilloscope which monitors an output from the photodetector to thereby measure a delay time of a gate trigger pulse supplied to a high-speed gate image intensifier; a pulse generator capable of independently and freely adjusting the delay time of two output pulses in synchronization with the laser pulse; a gate controller connected to the pulse generator and the oscilloscope; the high-speed gate image intensifier, intensifying and imaging the output of the multi-channel spectrometer, whose gate is opened over a time slot on the order of nanosecond by the gate controller; a CCD camera capturing an output image from the high-speed gate image intensifier; and a data-processing apparatus comprising a frame image data storage (frame grabber) which inputs spectroscopic image data of one frame from the CCD camera as a time-series analog signal, and converts the analog signal to a digital signal for transmission to a computer.
(2) A nanosecond time-gate spectroscopic diagnosis apparatus described in (1) above, wherein biological tissue is evaporated and excited by laser ablation, and spectra of a light emitting plume generated due to evaporation and excitation are detected at intervals on the order of nanosecond.
(3) A nanosecond time-gate spectroscopic diagnosis apparatus described in (1) above, wherein the light source is a laser light source which generates a nanosecond laser pulse within the UV range, the visible range, or the IR range.
(4) A nanosecond time-gate spectroscopic diagnosis apparatus described in (1) above, wherein the laser beam source is a flash-lamp-excited or semiconductor-laser-excited Q-switched Nd:YAG laser, or a semiconductor-laser-excited full-solid Q-switched Nd:YAG laser.
(5) A nanosecond time-gate spectroscopic diagnosis apparatus described in (1) above, wherein a laser beam from the light source includes light having a wavelength longer than the wavelength of a light emitting plume to be detected.
(6) A nanosecond time-gate spectroscopic diagnosis apparatus described in (1) above, wherein a shutter is disposed between the light source and the biological tissue, whereby a spectroscopic diagnosis of very low invasiveness is enabled through irradiation of the biological tissue with a single laser pulse.
(7) A nanosecond time-gate spectroscopic diagnosis apparatus described in (1) above, wherein the multi-channel spectrometer has a structure such that a light beam entering through an inlet slit is split, by use of a plurality of gratings, into a plurality of light beams corresponding to different wavelengths, and light beams having wavelengths within a particular range exit simultaneously from an exit opening at different angles.
(8) A nanosecond time-gate spectroscopic diagnosis apparatus described in (7) above, wherein the density of grating grooves of the grating is selectively set to 150/mm, 300/mm, 600/mm, or 1200/mm.
(9) A nanosecond time-gate spectroscopic diagnosis apparatus described in (7) above, wherein light beams having wavelengths within a particular range and exiting from the multi-channel spectrometer forms an image on pixels of the CCD camera.
(10) A nanosecond time-gate spectroscopic diagnosis apparatus described in (1) above, further comprising means for synchronizing operation of the high-speed gate image intensifier and operation of the CCD camera with a trigger pulse from the light source.
(11) A nanosecond time-gate spectroscopic diagnosis apparatus described in (1) above, wherein the biological tissue is biological hard tissue such as hair, a nail, or a tooth.
(12) A nanosecond time-gate spectroscopic diagnosis apparatus described in (1) above, wherein the biological tissue is biological soft tissue such as a vascular wall or subepidermal tissue.